AI Article Synopsis
- Immunotherapy is a promising cancer treatment that relies on immune cells in the tumor microenvironment, with "hot tumors" showing better results due to high immune cell presence.
- Previous research indicated that secretagogin (SCGN) decreases in expression as clear cell renal cell carcinoma (ccRCC) progresses, though it doesn't affect cancer cell traits directly.
- This study shows that SCGN can influence immune responses by regulating cytokine/chemokine secretion and attracting immune cells, particularly M1 macrophages, through the NF-κB signaling pathway, suggesting that maintaining SCGN expression could be a potential therapeutic strategy for ccRCC.
Article Abstract
Immunotherapy is considered to be one of the most promising curative modalities for cancer, and the effectiveness of immunotherapy depends on the abundance of immune cells in the tumor microenvironment (TME). Immunotherapy tends to be more effective in "hot tumors" characterized by a high abundant immune cells. Our previous studies found that secretagogin (SCGN) showed intranuclear aggregation in the early stages of clear cell renal cell carcinoma (ccRCC) development. However, with tumor progression and distant metastasis of the ccRCC, the expression of SCGN is gradually absent. In this study, we found that SCGN did not affect the malignant phenotype of cancer cells, but could regulate cytokine/chemokine secretion and immune cell migration by performing gene function assays and RNA-seq analyses after overexpressing SCGN in cell lines of ccRCC. Bioinformatics analysis, Transwell and co-culture experiments confirmed that ccRCC cells overexpressing SCGN could recruit M1-type macrophages. Mechanistically, SCGN initiates downstream cytokine/chemokine expression and secretion through the NF-κB signal pathway. This study provides a comprehensive understanding of the function of SCGN in ccRCC. Continuous forced expression of SCGN at different stages may be a potential approach for the treatment of ccRCC.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628334 | PMC |
| http://dx.doi.org/10.7150/ijbs.103252 | DOI Listing |
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